The intense research devoted over the last few years to the study of epilepsy and antiepileptic drugs (AEDs) has only dealt with the physiology of the disease. This quality research has been aimed to replace the older AEDs with broad activity profiles and several severe side effects with new AEDs with better defined mechanism of action and fewer side effects. Nevertheless, most of these drugs still produce serious adverse reactions, including among others, dizziness, ataxia, somnolence, headache, blurred vision, nausea, vomiting, skin, allergy and photosensitization. The molecular photochemical mechanisms for the photosensitizing ability of some AEDs has never been studied, even through it was reported over ten years ago. Recent studies on the laser flash phototysis of related neuroleptic drugs (imipramine) showed that the triplet state can be efficiently quenched by the protons in the solution. The effectiveness of the quenching is very sensitive to the structure of the drug and seems to be involve in their phototoxicity. We propose to perfor the same set of experiments on several phototoxic antiepileptics. The goal of this project is to measure the photophysicat properties of a selected group of tricydic antiepileptic drugs and to study their short-lived transients. Special attention will be given to those transients associated with adverse effects in vivo: the cation radical, the first triplet excited state and singlet oxygen, Basic UV-Vis and luminescence techniques will be employed to study their absorption/emission properties. The transients will be characterized using optical absorption measurements with a Nd-YAG laser set-up. For the triplet state of these compounds, the extinction coefficient and the quantum yield will be determined using a comparative method and the triplet-triplet energy transfer principle, respectively. The triplet state will be bleached with a second delayed pulse to elucidate the reaction mechanism of these u'ansients. Combined MM+/PM3/RHF theoretical calculations will be performed with HyperCHEM (TM) 7.0 on the whole set ofphotophysical parameters, The theoretical values will be correlated with the experimental ones. The major goal of this project is to find a molecular/photophysical descriptor for the phototoxic side effect of tricydic antiepileptics.